关键词: Autoimmune Diseases Biological Therapy Immune System Diseases Systemic vasculitis Therapeutics

Mesh : Humans Granulomatosis with Polyangiitis / complications drug therapy diagnosis Churg-Strauss Syndrome / complications drug therapy Retrospective Studies Prednisone / therapeutic use Treatment Outcome Asthma / drug therapy complications Eosinophilia / drug therapy complications Recurrence

来  源:   DOI:10.1136/ard-2023-224756

Abstract:
Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA.
We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm3.
Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268-4501) occurring at 13 weeks (IQR 4-36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab.
These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.
摘要:
背景:嗜酸细胞性肉芽肿伴多血管炎(EGPA)常与糖皮质激素依赖性哮喘和/或耳部相关,鼻喉(ENT)表现。当免疫抑制剂和/或美泊利单抗无效时,dupilumab可能是一种选择。我们描述了在复发和/或难治性EGPA中使用dupilumab的安全性和有效性。
方法:我们对接受dupilumab治疗的EGPA患者进行了一项多中心观察性研究。完全反应定义为伯明翰血管炎活动评分(BVAS)=0和泼尼松剂量≤4毫克/天,BVAS=0和泼尼松剂量>4mg/天的部分反应。嗜酸性粒细胞增多定义为嗜酸性粒细胞计数>500/mm3。
结果:纳入51例患者。dupilumab的主要适应症是92%的ENT症状。在中位随访13.1个月后,18例患者(35%)报告不良事件(AE),包括两个严重的AE。在34例患者中报告了嗜酸性粒细胞增多(67%),峰值2195/mm3(IQR1268-4501)出现在13周(IQR4-36),与41%的复发相关。21名患者(41%)获得完全响应,12名(24%)获得部分响应。16名(31%)患者在使用dupilumab时经历了EGPA复发,在14/16(88%)患者中与血嗜酸性粒细胞增多相关。复发患者开始dupilumab时的嗜酸性粒细胞计数中位数明显低于非复发患者,停止抗IL-5/IL-5R和改用dupilumab之间的中位时间也是如此.
结论:这些结果表明dupilumab可有效治疗EGPA相关的ENT表现。然而,三分之一的患者发生EGPA耀斑,88%的患者出现嗜酸性粒细胞增多。这表明需要谨慎。
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